CN1659162B - 三环凝血酶受体拮抗剂 - Google Patents

三环凝血酶受体拮抗剂 Download PDF

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Publication number
CN1659162B
CN1659162B CN038131129A CN03813112A CN1659162B CN 1659162 B CN1659162 B CN 1659162B CN 038131129 A CN038131129 A CN 038131129A CN 03813112 A CN03813112 A CN 03813112A CN 1659162 B CN1659162 B CN 1659162B
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alkyl
compound
nhc
independently
nhso
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Expired - Fee Related
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CN038131129A
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Chinese (zh)
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CN1659162A (zh
Inventor
S·查卡拉曼尼尔
M·C·克拉斯比
W·J·格林李
Y·王
Y·夏
E·P·维尔特里
M·切利亚
W·吴
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Merck Sharp and Dohme LLC
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Schering Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Neurosurgery (AREA)
  • Vascular Medicine (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN038131129A 2002-04-16 2003-04-14 三环凝血酶受体拮抗剂 Expired - Fee Related CN1659162B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US37307202P 2002-04-16 2002-04-16
US60/373,072 2002-04-16
PCT/US2003/011510 WO2003089428A1 (en) 2002-04-16 2003-04-14 Tricyclic thrombin receptor antagonists

Publications (2)

Publication Number Publication Date
CN1659162A CN1659162A (zh) 2005-08-24
CN1659162B true CN1659162B (zh) 2011-08-31

Family

ID=29250954

Family Applications (1)

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CN038131129A Expired - Fee Related CN1659162B (zh) 2002-04-16 2003-04-14 三环凝血酶受体拮抗剂

Country Status (34)

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US (3) US7304078B2 (no)
EP (5) EP1860106B1 (no)
JP (2) JP4558331B2 (no)
KR (1) KR101026929B1 (no)
CN (1) CN1659162B (no)
AR (1) AR039570A1 (no)
AT (3) ATE378330T1 (no)
AU (1) AU2003221932B2 (no)
BR (1) BRPI0309309B8 (no)
CA (1) CA2482858C (no)
CY (3) CY1107184T1 (no)
DE (3) DE60331114D1 (no)
DK (2) DK1495018T3 (no)
EC (1) ECSP045368A (no)
ES (3) ES2357876T3 (no)
FR (1) FR15C0047I2 (no)
HK (3) HK1070887A1 (no)
IL (1) IL164585A (no)
LT (1) LTC1495018I2 (no)
LU (1) LU92759I2 (no)
MX (1) MXPA04010308A (no)
MY (1) MY144040A (no)
NL (1) NL300746I2 (no)
NO (2) NO330500B1 (no)
NZ (2) NZ535880A (no)
PE (1) PE20040412A1 (no)
PL (1) PL214718B1 (no)
PT (2) PT1495018E (no)
RU (2) RU2329264C9 (no)
SG (1) SG164279A1 (no)
SI (2) SI1495018T1 (no)
TW (1) TWI343919B (no)
WO (1) WO2003089428A1 (no)
ZA (1) ZA200408342B (no)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106749201A (zh) * 2015-11-25 2017-05-31 博瑞生物医药（苏州）股份有限公司 一种沃拉帕沙及其中间体的制备方法

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US20040192753A1 (en) * 2000-06-15 2004-09-30 Samuel Chackalamannil Methods of use of thrombin receptor antagonists
US7235567B2 (en) * 2000-06-15 2007-06-26 Schering Corporation Crystalline polymorph of a bisulfate salt of a thrombin receptor antagonist
US7488742B2 (en) * 2000-06-15 2009-02-10 Schering Corporation Thrombin receptor antagonists
CA2567981C (en) * 2004-05-28 2010-08-31 Schering Corporation Constrained himbacine analogs as thrombin receptor antagonists
EP1799243B1 (en) * 2004-10-06 2015-07-15 University Of Rochester Treatment of pulmonary hypertension using an agent that inhibits a tissue factor pathway
US7541471B2 (en) * 2005-01-14 2009-06-02 Schering Corporation Synthesis of himbacine analogs
WO2006076565A2 (en) * 2005-01-14 2006-07-20 Schering Corporation Preparation of chiral propargylic alcohol and ester intermediates of himbacine analogs
DK1848705T3 (da) * 2005-01-14 2010-06-14 Schering Corp EXO- og diastereoselektive synteser af himbacin-analoger
EP2399912B1 (en) * 2005-01-14 2015-02-25 Merck Sharp & Dohme Corp. An exo-selective synthesis of himbacine analogs
EP1853592B1 (en) * 2005-01-14 2011-03-02 Schering Corporation Synthesis of himbacine analogs
TWI316937B (en) 2005-03-31 2009-11-11 Schering Corp Spirocyclic thrombin receptor antagonists
WO2007075808A2 (en) * 2005-12-20 2007-07-05 Schering Corporation Methods for preventing and/or treating a cell proliferative disorder
AU2006331583A1 (en) * 2005-12-22 2007-07-05 Schering Corporation Thrombin receptor antagonists as prophylaxis to complications from cardiopulmonary surgery
TW200812619A (en) * 2006-04-06 2008-03-16 Schering Corp TRA combination therapies
EP2007755B1 (en) * 2006-04-13 2012-06-27 Schering Corporation Fused ring thrombin receptor antagonists
JP2009542662A (ja) * 2006-06-29 2009-12-03 シェーリング コーポレイション 置換二環系および置換三環系トロンビン受容体アンタゴニスト
AR061727A1 (es) * 2006-06-30 2008-09-17 Schering Corp Sintesis de dietil [[ 5- ( 3-fluorofenil) -piridin -2il] metil] fosfonato
TWI367112B (en) * 2006-06-30 2012-07-01 Schering Corp Immediate-release tablet formulations of a thrombin receptor antagonist
DE102006036023A1 (de) 2006-08-02 2008-02-07 Sanofi-Aventis Imino-imidazo-pyridinderivate mit antithrombotischer Aktivität
TWI343262B (en) * 2006-09-26 2011-06-11 Schering Corp Rapidly disintegrating lyophilized oral formulations of a thrombin receptor antagonist
JP2010505842A (ja) 2006-10-04 2010-02-25 シェーリング コーポレイション トロンビン受容体拮抗薬としての二環式誘導体および三環式誘導体
CN101553484A (zh) * 2006-10-04 2009-10-07 先灵公司 以喜巴辛的被改质三环单位为基础的凝血酶受体拮抗剂
US20080194560A1 (en) * 2006-12-22 2008-08-14 Zhi Yun Wang Disintegration promoters in solid dose wet granulation formulations
JP2010522169A (ja) * 2007-03-23 2010-07-01 シェーリング コーポレイション トロンビン受容体アンタゴニストの使用による、経皮的インターベンション後の有害事象の低減
WO2009097971A1 (de) 2008-02-05 2009-08-13 Sanofi-Aventis Triazoliumsalze als par1-inhibitoren, ihre herstellung und verwendung als arzneimittel
PL2240487T3 (pl) 2008-02-05 2012-05-31 Sanofi Sa Triazolopirydazyny jako inhibitory PAR1, ich otrzymywanie i zastosowanie jako leków
WO2009124103A2 (en) * 2008-04-02 2009-10-08 Schering Corporation Combination therapies comprising par1 antagonists with par4 antagonists
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JP2012529431A (ja) 2009-06-08 2012-11-22 メルク・シャープ・アンド・ドーム・コーポレーション トロンビン受容体アンタゴニストおよびクロピドグレルの固定用量錠剤
US8609676B2 (en) 2009-08-04 2013-12-17 Merck Sharp & Dohme, Corp. 4, 5, 6-trisubstituted pyrimidine derivatives as factor IXa inhibitors
EP2558465B1 (de) 2010-04-16 2014-12-17 Sanofi Trizyklische pyridyl-vinyl-pyrrole als par1-inhibitoren
ES2527535T3 (es) 2010-04-16 2015-01-26 Sanofi Piridil-vinil-pirazolo-quinolinas como inhibidores de PAR1
KR101303348B1 (ko) 2010-06-25 2013-09-03 한국화학연구원 트롬빈 수용체 길항제인 ［6＋5］접합 바이사이클, 그의 제조방법 및 그를 포함하는 약제학적 조성물
US9340530B2 (en) 2012-03-06 2016-05-17 Merck Sharp & Dohme Corp. Preparation and use of bicyclic himbacine derivatives as PAR-1 receptor antagonists
WO2015013083A1 (en) * 2013-07-22 2015-01-29 Merck Sharp & Dohme Corp. Co-crystal of the par-1 receptor antagonist vorapaxar and aspirin
US20160200715A1 (en) * 2013-08-22 2016-07-14 Merck Sharp & Dohme Corp. Preparation and use of 7a-heterocycle substituted- 6,6-difluoro bicyclic himbacine derivatives as par-1 receptor antagonists
US9808473B2 (en) 2013-08-22 2017-11-07 Merck Sharp & Dohme Corp. Preparation and use of 3-pyridyl substituted-6,6-difluoro bicyclic himbacine derivatives as par-1 receptor antagonists
US9701669B2 (en) 2013-08-22 2017-07-11 Merck Sharp & Dohme Corp. Preparation and use of 7a-amide substituted- 6,6-difluoro bicyclic himbacine derivatives as PAR-1 receptor antagonists
FR3014693B1 (fr) 2013-12-16 2016-01-08 Pf Medicament Utilisation de la 3-(2-chloro-phenyl)-1-[4-(4-fluoro-benzyl)-piperazin-1-yl]-propenone pour la prevention et/ou le traitement des pathologies fonctionnelles pelvi-perineales
EP3131897B8 (en) 2014-04-16 2022-08-03 Merck Sharp & Dohme LLC Factor ixa inhibitors
DE102014108210A1 (de) 2014-06-11 2015-12-17 Dietrich Gulba Rodentizid
CN105985303B (zh) * 2015-02-13 2020-08-14 上海彩迩文生化科技有限公司 抗凝血剂的制备方法、中间体及其制备方法
CN106478608A (zh) * 2015-09-01 2017-03-08 博瑞生物医药（苏州）股份有限公司 沃拉帕沙的硫酸盐的结晶多晶型物
WO2017134200A1 (en) * 2016-02-05 2017-08-10 Sanovel Ilac Sanayi Ve Ticaret A.S. A novel pharmaceutical composition of vorapaxar and metoprolol
TR201601548A2 (tr) * 2016-02-05 2018-03-21 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Vorapaksar ve metoprololün bi̇r farmasöti̇k kompozi̇syonu
TW201738221A (zh) * 2016-04-22 2017-11-01 Jiangsu Tasly Diyi Pharmaceutical Co Ltd 新的喜巴辛類似物、其藥物組合物及其在醫藥中的應用
CN106236779A (zh) * 2016-08-22 2016-12-21 孔五 一种脐带血富血小板血浆prp的制备方法
FR3090317B1 (fr) 2018-12-19 2021-05-07 Cvasthera Utilisation d’un antagoniste de par-1 pour le traitement d’une maladie inflammatoire chronique intestinale
CN110407819B (zh) * 2019-08-02 2020-06-26 牡丹江医学院 一种作为预防外科手术并发症的凝血酶受体拮抗剂
US20210113536A1 (en) * 2019-10-21 2021-04-22 United States Government as Represented by the Department of Veteran Affairs Methods and compositions for detecting and treating venous thromboembolism
FR3109089B1 (fr) 2020-04-08 2023-04-14 Cvasthera Composition pharmaceutique pour le traitement des maladies inflammatoires intestinales
EP4185587A1 (en) 2020-07-22 2023-05-31 JANSSEN Pharmaceutica NV Compounds useful as factor xia inhibitors
US11845748B2 (en) 2021-03-18 2023-12-19 Janssen Pharmaceutica Nv Bicyclic pyridine N-oxide derivatives useful as a factor XIa inhibitors
US11919881B2 (en) 2021-03-18 2024-03-05 Janssen Pharmaceutica Nv Substituted pyridine N-oxide derivatives useful as a factor XIa inhibitors
US11814364B2 (en) 2021-03-18 2023-11-14 Janssen Pharmaceutica Nv Pyridine N-oxide derivatives useful as factor XIa inhibitors
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US11897880B2 (en) 2021-04-30 2024-02-13 Janssen Pharmaceutica Nv 7,8-dihydrobenzo[e]pyrido[3,4-c]azocine-2,5(3H,6H)-dione derivatives useful as a factor XIa inhibitors
US11958856B2 (en) 2021-07-22 2024-04-16 Janssen Pharmaceutica Nv Substituted 1,2,3,8,9,9a-hexahydro-5H-pyrrolo[1,2-a]azepin-5-ones as factor XIa inhibitors
FR3134314A1 (fr) 2022-04-08 2023-10-13 Cvasthera Composition pharmaceutique à base de vorapaxar et son utilisation pour le traitement des maladies inflammatoires intestinales

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Cited By (1)

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Publication number Priority date Publication date Assignee Title
CN106749201A (zh) * 2015-11-25 2017-05-31 博瑞生物医药（苏州）股份有限公司 一种沃拉帕沙及其中间体的制备方法

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PL214718B1 (pl) 2013-09-30
LU92759I2 (en) 2015-08-31
CY2015029I2 (el) 2016-04-13
EP1495018B3 (en) 2011-03-16
KR20040099441A (ko) 2004-11-26
EP1982984A3 (en) 2008-10-29
NO2015016I1 (no) 2015-07-20
CA2482858A1 (en) 2003-10-30
EP1982984B1 (en) 2013-02-13
TW200404068A (en) 2004-03-16
ATE378330T1 (de) 2007-11-15
JP2010132710A (ja) 2010-06-17
NO2015016I2 (no) 2015-07-09
BRPI0309309B1 (pt) 2018-09-04
ZA200408342B (en) 2006-05-31
NL300746I1 (no) 2016-01-21
EP2065384A1 (en) 2009-06-03
ES2357876T3 (es) 2011-05-03
CY1107184T1 (el) 2012-10-24
EP2062890B1 (en) 2011-01-05
RU2004133375A (ru) 2005-07-10
CY1111363T1 (el) 2015-08-05
NZ535880A (en) 2007-11-30
DE60331114D1 (de) 2010-03-11
IL164585A0 (en) 2005-12-18
IL164585A (en) 2010-11-30
CA2482858C (en) 2010-11-30
NZ575139A (en) 2010-08-27
CN1659162A (zh) 2005-08-24
EP1860106A1 (en) 2007-11-28
DK2065384T3 (da) 2011-05-02
NO330500B1 (no) 2011-05-02
PE20040412A1 (es) 2004-07-12
LTC1495018I2 (lt) 2017-04-10
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